Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers develop gene therapy to reverse pulmonary arterial hypertension

06.06.2005


A University of Alberta research team has discovered important new information they hope will lead to more effective treatments for pulmonary arterial hypertension (PAH)--a deadly form of high blood pressure in the pulmonary arteries caused by uncontrolled cell growth. Therapies are currently limited for a disease that can lead to heart failure and death within a few years.



The researchers have shown that Survivin, a protein almost exclusively expressed in cancer, is also heavily expressed in both human and animal lung arteries with PAH. Survivin is an inhibitor of apoptosis--or programmed cell death--which promotes cancer by suppressing the body’s ability to limit excessive cell growth.

Armed with this new information and using animal models, the researchers developed a nebulized and inhaled gene therapy to deliver an inactive Survivin-mutant via a virus--known in science as a "dominant negative construct"--effectively inhibiting endogenous Survivin. The therapy reversed PAH in rats and improved their heart function and their survival, thus holding out some promising avenues of treatment for human PAH. The team members believe that as in cancer, Survivin drives excessive cell growth in the PAH lung blood vessels.


"The most intriguing aspect," explains principal researcher Evangelos Michelakis, "is we’ve shown for the first time that this cancer protein is also expressed within the blood vessels of the lung in patients suffering with PAH, but not in normal human blood vessels, making survivin a very attractive target for selective intervention.

"This makes the proliferation of lung blood vessels in this disease a ’form of cancer’ or a form of neoplasia to be more precise, first proposed by Drs. Voelkel and Tuder from the University of Colorado. We’ve demonstrated for the first time that, like cancer, apoptosis is suppressed in the lung blood vessel wall in this disease."

"Our biggest challenge in treating PAH is the fact we don’t know what makes the cells in the lung blood vessel wall grow excessively," says the University of Alberta cardiology professor and Canada Research Chair holder. "And therapies also have to target the lung blood vessels and spare the normal cells in the rest of the body."

The paper is entitled Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. It’s published in the June issue of The Journal of Clinical Investigation. In an accompanying editorial entitled Lessons learned from cancer may help in the treatment of pulmonary hypertension, written by French researcher Serge Adnot, the journal stated: "These findings raise important issues regarding the role of survivin in the pathogenesis of PAH, its value as a prognostic indicator, and its use as a target for new therapeutic strategies."

Other authors include: Sean McMurtry, Pulmonary Hypertension Program; Stephen Archer, Canada Research Chair in Translational Cardiovascular Research; Dario Altieri, Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School; Sebastien Bonnet, Alois Haromy, Gwyneth Harry and Sandra Bonnet, the Vascular Biology Group and Pulmonary Hypertension Program; and Lakshmi Puttagunta, Department of Laboratory Medicine and Pathology, U of A.

The latest research builds on previous work by the group, published a few months ago in Circulation Research, showing that an orally available drug, Dichloroacetate, selectively enhances apoptosis in PAH and thus reverses PAH, prolonging the survival of rats. Because this oral therapy has already been tried in humans with congenital mitochondrial diseases, the team is initiating a clinical trial in human PAH. Similarly, newer drugs that inhibit Survivin, currently in trials in oncology, might also be directly applicable to PAH patients, Dr. Michelakis explains.

The researchers are supported by the Canadian Institutes of Health Research and Canada Research Chair Program, the Alberta Heart and Stroke Foundation, the Alberta Heritage Foundation for Medical Research, the Canadian Institutes of Health Research, the National Institutes of Health, and the Alberta Cardiovascular and Stroke Research Centre (ABACUS). Dr. McMurtry is supported by the University’s clinician investigator program and TORCH, a CIHR-sponsored multidisciplinary training program in cardiovascular disease, and a training grant from Bristol-Myers Squibb Company.

Michael Robb | EurekAlert!
Further information:
http://www.ualberta.ca

More articles from Health and Medicine:

nachricht Hot cars can hit deadly temperatures in as little as one hour
24.05.2018 | Arizona State University

nachricht 3D images of cancer cells in the body: Medical physicists from Halle present new method
16.05.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>